Novel aurone-derived piperazine sulfonamides: Development and mechanisms of action as immunostimulants against plant bacterial diseases.

Bacterial diseases pose a significant threat to the sustainable production of crops. Given the unsatisfactory performance and poor eco-compatibility of conventional bactericides, here we present a series of newly structured bactericides that are inspiringly designed by aurone found in plants of the Asteraceae family. These aurone-derived compounds contain piperazine sulfonamide motifs and have shown promising in vitro performance against Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicola and Xanthomonas axonopodis pv. citri, in particular, compound II23 achieved minimum half-maximal effective concentrations of 1.06, 0.89, and 1.78 µg/mL, respectively. In vivo experiments conducted in a greenhouse environment further revealed that II23 offers substantial protective and curative effects ranging between 68.93 and 70.29% for rice bacterial leaf streak and 53.17-64.43% for citrus bacterial canker, which stands in activity compared with lead compound aurone and commercial thiodiazole copper. Additional physiological and biochemical analyses, coupled with transcriptomics, have verified that II23 enhances defense enzyme activities and chlorophyll levels in rice. Significantly, it also stimulates the accumulation of abscisic acid (ABA) and upregulates the expression of key genes OsPYL/RCAR5, OsBIPP2C1, and OsABF1, thereby activating the ABA signaling pathway in rice plants under biological stress from bacterial infections.

Toward Diverse or Standardized: A Systematic Review Identifying Transcutaneous Stimulation of Auricular Branch of the Vagus Nerve in Nomenclature.

OBJECTIVES: After 20 years of development, there is confusion in the nomenclature of transcutaneous stimulation of the auricular branch of the vagus nerve (ABVN). We performed a systematic review of transcutaneous stimulation of ABVN in nomenclature. MATERIALS AND METHODS: A systematic search of the literature was carried out, using the bibliographic search engine PubMed. The search covered articles published up until June 11, 2020. We recorded the full nomenclature and abbreviated nomenclature same or similar to transcutaneous stimulation of ABVN in the selected eligible studies, as well as the time and author information of this nomenclature. RESULTS: From 261 studies, 67 full nomenclatures and 27 abbreviated nomenclatures were finally screened out, transcutaneous vagus nerve stimulation and tVNS are the most common nomenclature, accounting for 38.38% and 42.06%, respectively. In a total of 97 combinations of full nomenclatures and abbreviations, the most commonly used nomenclature for the combination of transcutaneous vagus nerve stimulation and tVNS, accounting for 30.28%. Interestingly, the combination of full nomenclatures and abbreviations is not always a one-to-one relationship, there are ten abbreviated nomenclatures corresponding to transcutaneous vagus nerve stimulation, and five full nomenclatures corresponding to tVNS. In addition, based on the analysis of the usage habits of nomenclature in 21 teams, it is found that only three teams have fixed habits, while other different teams or the same team do not always use the same nomenclature in their paper. CONCLUSIONS: The phenomenon of confusion in the nomenclature of transcutaneous stimulation of ABVN is obvious and shows a trend of diversity. The nomenclature of transcutaneous stimulation of ABVN needs to become more standardized in the future.

Comparative Effectiveness of Transcutaneous Auricular Vagus Nerve Stimulation vs Citalopram for Major Depressive Disorder: A Randomized Trial.

OBJECTIVES: Major depressive disorder (MDD) is one of the most common mental illnesses. This study aims to investigate the effectiveness of transcutaneous auricular vagus nerve stimulation (taVNS) compared with the effectiveness of citalopram, a commonly used antidepressant, in patients with depression. MATERIAL AND METHODS: A total of 107 male and female patients with MDD (55 in the taVNS group and 52 in the citalopram group) were enrolled in a prospective 12-week, single-blind, comparative effectiveness trial. Participants were recruited from the outpatient departments of three hospitals in China. Participants were randomly assigned to either taVNS treatment (eight weeks, twice per day, with an additional four-week follow-up) or citalopram treatment (12 weeks, 40 mg/d). The primary outcome was the 17-item Hamilton Depression Rating Scale (HAM-D17) measured every two weeks by trained interviewers blinded to the treatment assignment. The secondary end points included the 14-item Hamilton Anxiety Scale and peripheral blood biochemical indexes. RESULTS: The HAM-D17 scores were reduced in both treatment groups; however, there was no significant group-by-time interaction (95% CI: -0.07 to 0.15, p = 0.79). Nevertheless, we found that taVNS produced a significantly higher remission rate at week four and week six than citalopram. Both treatments were associated with significant changes in the peripheral blood levels of 5-hydroxytryptamine, dopamine, γ-aminobutyric acid, and noradrenaline, but there was no significant difference between the two groups. CONCLUSION: taVNS resulted in symptom improvement similar to that of citalopram; thus, taVNS should be considered as a therapeutic option in the multidisciplinary management of MDD. Nevertheless, owing to the design of this study, it cannot be ruled out that the reduction in depression severity in both treatment groups could be a placebo effect.

Mechanisms underlying antidepressant effect of transcutaneous auricular vagus nerve stimulation on CUMS model rats based on hippocampal α7nAchR/NF-κB signal pathway.

BACKGROUND: Stress-induced neuroinflammation was considered to play a critical role in the pathogenesis of depression. Transcutaneous auricular vagus nerve stimulation (taVNS) is a relatively non-invasive alternative treatment for patients suffering from major depressive disorder. The anti-inflammatory signal of vagus nerve is mediated by α7 nicotinic acetylcholine receptor (α7nAchR), and the hippocampus, the region with the most distribution of α7nAchR, regulates emotions. Here, we investigated the role of α7nAchR mediating hippocampal neuroinflammation in taVNS antidepressant effect though homozygous α7nAChR (-/-) gene knockout and α7nAchR antagonist (methyllycaconitine, MLA). METHODS: There were control, model, taVNS, α7nAChR(-/-) + taVNS, hippocampus (Hi) MLA + taVNS and Hi saline + taVNS groups. We used the chronic unpredicted mild stress (CUMS) method to establish depressive model rats for 42 days, excepting control group. After the successful modeling, except the control and model, the rats in the other groups were given taVNS, which was applied through an electroacupuncture apparatus at the auricular concha (2/15 Hz, 2 mA, 30 min/days) for 21 days. Behavioral tests were conducted at baseline, after modeling and after taVNS intervention, including sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST). These tests are widely used to evaluate depression-like behavior in rats. The samples were taken after experiment, the expressions of α7nAchR, NF-κB p65, IL-1ß and the morphology of microglia were detected. RESULTS: Depression-like behavior and hippocampal neuroinflammation in CUMS model rats were manifested by down-regulated expression of α7nAchR, up-regulated expression of NF-κB p65 and IL-1ß, and the morphology of microglia was in amoebic-like activated state. TaVNS could significantly reverse the above-mentioned phenomena, but had rare improvement effect for α7nAChR(-/-) rats and Hi MLA rats. CONCLUSION: The antidepressant effect of taVNS is related to hippocampal α7nAchR/NF-κB signal pathway.

Engineering and Application of a Myoglobin Binding Split Aptamer.

Given that a split aptamer provides a chance for the development of a sandwich assay for targets with only one aptamer, it has received extensive attention in biosensing. However, due to the lack of binding mechanisms and reliable methods, there were still a few split aptamers that bind to proteins. In this work, cardiac biomarker myoglobin (Myo) was selected as a model, a new strategy of engineering split aptamers was explored with atomic force spectroscopy (AFM), and split aptamers against target protein could be achieved by choosing the optimal binding probability between split aptamers and target. Then, the obtained split aptamers were designed for Myo detection based on dynamic light scattering (DLS). The results demonstrated that the obtained split aptamers could be used to detect targets in human serum. The strategy of engineering split aptamers has the advantages of being intuitive and reliable and could be a general strategy for obtaining split aptamers.

Exploring Interactions of Aptamers with Aß40 Amyloid Aggregates and Its Application: Detection of Amyloid Aggregates.

The exhaustive investigating interactions between recognition probes and amyloid aggregates, especially simultaneous recognition events, are challenging and crucial for the design of biosensing probes and further diagnosis of amyloid diseases. In the present work, the interactions of aptamers (Apts) with ß-amyloid (Aß) aggregates were explored thoroughly by single-molecule force spectroscopy (SMFS). Indeed, it was found that the interaction of aptamer1 (Apt1)-amyloid aggregates was different from that of aptamer2 (Apt2)-Aß40 aggregates at the single-molecule level. Especially, the interaction force of Apt1-Aß40 fibril showed a double distinguishing Gaussian fitting. The only unimodal distribution of the force histogram was displayed for the interactions of Apt2-Aß40 oligomer, Apt2-Aß40 fibril, and Apt1-Aß40 oligomer. More intriguingly, two Apts could bind to amyloid aggregates simultaneously. With the assistance of two Apts recognition, a novel sensitive dual Apt-based surface plasmon resonance (SPR) sensor using Au nanoparticles (AuNPs) was developed for quantifying Aß40 aggregates. The dual Apt-based SPR sensor not only avoided the limitation of steric hindrance and epitope but also employed simple operation as well as inexpensive recognition probes. A detection limit as low as 0.2 pM for Aß40 oligomer and 0.05 pM for Aß40 fibril could be achieved. Moreover, the established sensor could be successfully applied to detect Aß40 aggregates in artificial cerebrospinal fluid (CSF) and undiluted real CSF. This work could provide a strategy to monitor a simultaneous recognition event using SMFS and broaden the application of Apts in the diagnosis of neurodegenerative diseases.

Investigation of the interaction between split aptamer and vascular endothelial growth factor 165 using single molecule force spectroscopy.

Understanding the binding of split aptamer/its target could become a breakthrough in the application of split aptamer. Herein, vascular endothelial growth factor (VEGF), a major biomarker of human diseases, was used as a model, and its interaction with split aptamer was explored with single molecule force spectroscopy (SMFS). SMFS demonstrated that the interaction force of split aptamer/VEGF165 was 169.44 ± 6.59 pN at the loading rate of 35.2 nN/s, and the binding probability of split aptamer/VEGF165 was dependent on the concentration of VEGF165 . On the basis of dynamic force spectroscopy results, one activation barrier in the dissociation process of split aptamer/VEGF165 complexes was revealed, which was similar to that of the intact aptamer/VEGF165 . Besides, the dissociation rate constant (koff ) of split aptamer/VEGF165 was close to that of intact aptamer/VEGF165 , and the interaction force of split aptamer/VEGF165 was higher than the force of intact aptamer/VEGF165 . It indicated that split aptamer also possessed high affinity with VEGF165 . The work can provide a new method for exploring the interaction of split aptamer/its targets at single-molecule level.

Novel vanillin derivatives containing a 1,3,4-thiadiazole moiety as potential antibacterial agents.

In this study, thirty-four novel vanillin derivatives containing a 1,3,4-thiadiazole structure were obtained and their antibacterial activities were evaluated. The results indicate that most of the title compounds displayed inhibitory effects on Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc). Among them, compound 29 exhibited excellent antibacterial activities against Xoo and Xoc in vitro, with the EC50 values of 3.14 and 8.83 µg/mL, respectively, much superior to thiodiazole copper (87.03 and 108.99 µg/mL) and bismerthiazol (67.64 and 79.26 µg/mL). Under greenhouse condition, the protective efficiency of compound 29 against rice bacterial leaf blight was 49.34%, and curative efficiency was 40.96%. In addition, compound 29 can reduce the exopolysaccharides production of Xoo, increase the permeability of cell membrane and damage cell membrane.

Effects of Transcutaneous Auricular Vagus Nerve Stimulation on Peripheral and Central Tumor Necrosis Factor Alpha in Rats with Depression-Chronic Somatic Pain Comorbidity.

Depression and pain disorders share a high degree of comorbidity. Inflammatory mechanisms play an important role in the pathogenesis of depression-chronic somatic pain comorbidity. In this study, we investigated the effects of acupuncture on blood and brain regional tumor necrosis factor alpha (TNF-α) in rats with depression and chronic somatic pain comorbidity. Forty Sprague-Dawley rats were randomly divided into the following 4 groups with 10 each: control, model, model treated with transcutaneous auricular vagus nerve stimulation (taVNS), and model treated with electroacupuncture (EA). Chronic unpredictable mild stress (CUMS) with chronic constriction injury of the sciatic nerve (CCI) was used to produce depression and chronic somatic pain comorbidity in the latter 3 groups. The rats of the taVNS and EA groups received, respectively, taVNS and EA at ST 36 for 28 days. Pain intensity was measured using a mechanical withdrawal threshold and thermal stimulation latency once biweekly. Depressive behavior was examined using a sucrose preference test at baseline and the end of modeling and intervention. The level of plasma TNF-α and the expression of TNF-α in the prefrontal cortex (PFC), hippocampus, amygdala, and hypothalamus were measured. While CUMS plus CCI produced remarkable depression-like behavior and pain disorders, EA and taVNS significantly improved depression and reduced pain intensity. CUMS plus CCI also resulted in a significant increase in plasma TNF-α level and the expression in all brain regions examined compared to the intact controls. Both EA and taVNS interventions, however, suppressed the elevated level of TNF-α. These results suggest that EA and taVNS have antidepressant and analgesic effects. Such effects may be associated with the suppression of TNF-α-related neuroinflammation.

Discovery of novel bis-sulfoxide derivatives bearing acylhydrazone and benzothiazole moieties as potential antibacterial agents.

On the basis of the active substructure combination principle, 24 novel synthesis of novel bis-sulfoxide derivatives bearing acylhydrazone and benzothiazole moieties as potential antibacterial agents were designed and synthesized. The bioactivity assay results showed that many compounds had significant in vitro inhibitory effects against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas citri pv. citri (Xac). Notably, compound 4b had the best in vitro antibacterial activity against Xoo at an half-maximal effective concentration value of 11.4 µg/mL, which was superior to those of thiodiazole copper (TDC) and bismerthiazol (BMT). Compared with TDC and BMT, compound 4b was more effective in vivo controlling rice bacterial leaf blight with curative and protection activities of 42.5% and 40.3%, respectively. In addition, compound 4b can influence biofilm formation, inhibit extracellular polysaccharide production, and ultimately reduce the pathogenicity of Xoo. All the results indicated that bis-sulfoxide derivatives bearing acylhydrazone and benzothiazole moieties can be used for the development of small-molecule pesticides with high antibacterial activity.

Surface plasmon resonance assay for exosomes based on aptamer recognition and polydopamine-functionalized gold nanoparticles for signal amplification.

A novel surface plasmon resonance (SPR) strategy is introduced for the specific determination of exosomes based on aptamer recognition and polydopamine-functionalized gold nanoparticle (Au@PDA NP)-assisted signal amplification. Exosomes derived from hepatic carcinoma SMMC-7721 were selected as the model target. SMMC-7721 exosomes can be specifically captured by the aptamer ZY-sls that was complementary to the DNA tetrahedron probes (DTPs), and then the CD63 aptamer-linked Au@PDA NPs recognized SMMC-7721 exosomes for signal amplification. The DTPs were modified on a Au film for preventing Au deposition on the surface during the introduction of HAuCl4, and PDA coated on the AuNPs was used to reduce HAuCl4 in situ without any reductant assistance. It results in a further enhanced SPR signal. The assay can clearly distinguish SMMC-7721 exosomes from others (HepG2 exosomes, Bel-7404 exosomes, L02 exosomes, MCF-7 exosomes, and SW480 exosomes, respectively). SMMC-7721 exosomes are specifically determined as low as 5.6 × 105 particles mL-1. The method has successfully achieved specific determination of SMMC-7721 exosomes even in 50% of human serum without any pretreatment. Graphical abstract A novel surface plasmon resonance (SPR) strategy was introduced for the specific determination of exosomes based on aptamer recognition and polydopamine functionalized gold nanoparticles (Au@PDA NPs). The SPR signal was improved using the Au@PDA NPs assisted amplification.

Novel amide derivatives containing 1,3,4-thiadiazole moiety: Design, synthesis, nematocidal and antibacterial activities.

A series of novel amide derivatives containing 1,3,4-thiadiazole moiety were synthesized and their bioactivities were evaluated. The compound 34 exhibited good nematocidal activities against Meloidogyne incognita in vitro and in vivo, the LC50 value and control effect were 6.5 mg/L and 83.3%, respectively. Meanwhile, it exhibited exciting antibacterial activities against Xanthomonas oryzae pv. oryzae, Xanthomonas campestris pv. citri, and Ralstonia solanacearum, the EC50 values were 0.4, 6.7 and 5.1 mg/L, respectively, which were better than positive controls. The curative and protection activities under the greenhouse conditions of compound 34 against rice bacterial blight were 47.9 and 55.8%, respectively. The structure-activity relationship were analyzed in detail.

Novel 1,3,4-Oxadiazole Derivatives Containing a Cinnamic Acid Moiety as Potential Bactericide for Rice Bacterial Diseases.

Rice bacterial leaf blight and leaf streak are two important bacterial diseases of rice, which can result in yield loss. Currently, effective antimicrobials for rice bacterial diseases are still lacking. Thus, to develop highly effective and low-risk bactericides, 31 novel 1,3,4-oxadiazole derivatives containing a cinnamic acid moiety were designed and synthesized. Bioassay results demonstrated that all compounds exhibited good antibacterial activities in vitro. Significantly, compounds 5r and 5t showed excellent antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) and X. oryzae pv. oryzicola (Xoc), with the 50% effective concentration (EC50) values of 0.58 and 0.34, and 0.44 and 0.20 µg/mL, respectively. These compounds were much better than thiodiazole copper (123.10 and 161.52 µg/mL) and bismerthiazol (85.66 and 110.96 µg/mL). Moreover, compound 5t had better protective and curative activities against rice bacterial leaf blight and leaf streak than thiodiazole copper and bismerthiazol in vivo. Simultaneously, the in vivo efficacy of the compounds was demonstrated by real-time quantitative PCR to quantify bacterial titers. In addition, a three-dimensional quantitative structure⁻activity relationship model was created and presented good predictive ability. This work provides support for 1,3,4-oxadiazole derivatives containing a cinnamic acid moiety as a potential new bactericide for rice bacterial diseases.

De Novo Mutated TUBB2B Associated Pachygyria Diagnosed by Medical Exome Sequencing and Long-Range PCR.

INTRODUCTION: A range of cerebrocortical development malformations (MCD) ranging from simplified gyral patterns to the complete loss of gyri and sulci is associated with mutations in a cluster of highly homolog ß-tublin genes, such as TUBB2A and TUBB2B. CASE REPORT: The fetus had pachygyria, asymmetrical perisylvian polymicrogyria, dysplasia of the lateral sulcus and insula, agenesis of the splenium and partial agenesis of the body corpus callosum, cerebellar superior vermian hypoplasia with agenesis of the inferior vermis. Karyotype and microarray were normal. Trio Medical Exome Sequencing detected a de novo novel heterozygous mutation c.862G > A (p.E288K) in the tubulinpathy genes. Long-range PCR and Sanger sequencing specific for TUBB2A and TUBB2B gene detected a heterozygous variant c.862G > A specific to TUBB2B. CONCLUSION: The combination of LR-PCR amplification and medical exome sequencing allows mutational assessment in tubulinopathy genes. Our study expands the spectrum of malformations associated with mutations in the ß-tubulin gene TUBB2B.

Auricular vagus nerve stimulation enhances central serotonergic function and inhibits diabetic neuropathy development in Zucker fatty rats.

Painful neuropathy is a frequent comorbidity in diabetes. Zucker diabetic fatty (fa/fa) rats develop type 2 diabetes spontaneously with aging and show nociceptive hypersensitivity at the age of 13 weeks. In preclinical and clinical studies, the treatment of diabetic neuropathy is challenging, but complementary medicine such as transcutaneous auricular vagus nerve stimulation (taVNS) appears beneficial to the relief of neuropathic pain. However, the mechanism behind the effectiveness of taVNS remains unclear. In this study, we show that daily 30-min taVNS (2/15 Hz, 2 mA) for consecutive 27 days effectively inhibited the development of nociceptive hypersensitivity in Zucker diabetic fatty rats as detected by thermal hyperalgesia and mechanical allodynia in hindpaw. We also demonstrated that this beneficial effect in nociceptive behavior is related to an elevated serotonin (5-HT) plasma concentration and an upregulated expression of 5-HT receptor type 1A (5-HT1AR) in hypothalamus. We conclude that daily 30-min taVNS sessions lessen diabetic neuropathy development by enhancing serotonergic function in genetically diabetes prone individuals. Perspective This article presents taVNS as a new approach to inhibit the development of diabetic neuropathy in genetically prone individuals. This approach could potentially help clinicians who seek to avoid the complication of neuropathic pain in diabetic patient or to relieve the pain if there was one.

Identification of a novel DNMT1 mutation in a Chinese patient with hereditary sensory and autonomic neuropathy type IE.

BACKGROUND: DNA methyltransferase 1 (EC 2.1.1.37), encoded by DNMT1 gene, is one of key enzymes in maintaining DNA methylation patterns of the human genome. It plays a crucial role in embryonic development, imprinting and genome stability, cell differentiation. The dysfunction of this group of enzymes can lead to a variety of human genetic disorders. Until now, mutations in DNMT1 have been found to be associated with two distinct phenotypes. Mutations in exon 20 of this gene leads to hereditary sensory and autonomic neuropathy type IE, and mutations in exon 21 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy. CASE PRESENTATION: Here we report a novel DNMT1 mutation in a sporadic case of a Chinese patient with cerebellar ataxia, multiple motor and sensory neuropathy, hearing loss and psychiatric manifestations. Furthermore, we elucidated its pathogenic effect through molecular genetics studies and revealed that this defective DNMT1 function is responsible for the phenotypes in this individual. CONCLUSION: Our findings expand the spectrum of DNMT1-related disorders and provide a good example of precision medicine through the combination of exome sequencing and clinical testing.

A Rare Hb H Hydrops Fetalis Syndrome Caused by the - -SEA Deletion in Combination with the Rare Hb Hirosaki Mutation in a Chinese Patient.

Despite the milder clinical severity of Hb H patients compared with those of Hb Bart's hydrops fetalis or patients with ß-thalassemia major (ß-TM), a few cases of Hb H hydrops fetalis syndrome have been reported so far. Here, we describe, for the first time in the Chinese population, one case of a neonate with Hb H hydrops fetalis syndrome caused by the - -SEA (Southeast Asian) deletion in combination with the Hb Hirosaki (HBA2: c.132C>G, p.Phe43Leu) mutation. Our study highlights the importance of continuous fetal monitoring using ultrasonography and blood screening studies of fetuses. Appropriate genetic counseling and comprehensive clinical follow-up should be performed on a pregnant woman who carried an α0-thalassemia (α0-thal) deletion and had a Hb H or Hb Bart's hydrops fetalis offspring, especially if the woman's partner also carried a hemoglobinopathy.

MiR-503 promotes the migration and invasion of colorectal cancer cells by regulating PDCD4.

PURPOSE: MicroRNAs are expressed abnormally in colorectal cancer (CRC) and could participate in its development. In this study we aimed to explore the molecular mechanisms of miR-503 in the genesis of CRC. METHODS: The relative expression of miR-503 and programmed cell death 4 (PDCD4) tumor suppressor in CRC tissues and cell lines were detected by qRT-PCR and Western blot. Cell migration and cell invasion were assessed by transwell assay. Moreover, the confirmation of the direct target of miR-503 in CRC was performed by luciferase reporter assay. RESULTS: The expression of miR-503 was increased remarkably in CRC, while PDCD4 decreased. Moreover, PDCD4 was verified as a specific target of miR-503 in CRC and it could reverse the effect of miR-503 on CRC cells. Furthermore, the abnormal expression of miR-503 played an important role in regulating of the development of CRC cells. In addition, PDCD4 protein expression and miR-503 mRNA expression were negatively correlated in CRC tissues. CONCLUSION: The inhibitory effect of miR-503 in CRC was realized by the upregulation of PDCD4, suggesting that miR-503/PDCD4 axis might play a critical role in CRC and could possibly be a therapeutic target.

Allele-specific induction of IL-1ß expression by C/EBPß and PU.1 contributes to increased tuberculosis susceptibility.

Mycobacterium tuberculosis infection is associated with a spectrum of clinical outcomes, from long-term latent infection to different manifestations of progressive disease. Pro-inflammatory pathways, such as those controlled by IL-1ß, have the contrasting potential both to prevent disease by restricting bacterial replication, and to promote disease by inflicting tissue damage. Thus, the ultimate contribution of individual inflammatory pathways to the outcome of M. tuberculosis infection remains ambiguous. In this study, we identified a naturally-occurring polymorphism in the human IL1B promoter region, which alters the association of the C/EBPß and PU.1 transcription factors and controls Mtb-induced IL-1ß production. The high-IL-1ß expressing genotype was associated with the development of active tuberculosis, the severity of pulmonary disease and poor treatment outcome in TB patients. Higher IL-1ß expression did not suppress the activity of IFN-γ-producing T cells, but instead correlated with neutrophil accumulation in the lung. These observations support a specific role for IL-1ß and granulocytic inflammation as a driver of TB disease progression in humans, and suggest novel strategies for the prevention and treatment of tuberculosis.

BDS/GPS Dual Systems Positioning Based on the Modified SR-UKF Algorithm.

The Global Navigation Satellite System can provide all-day three-dimensional position and speed information. Currently, only using the single navigation system cannot satisfy the requirements of the system's reliability and integrity. In order to improve the reliability and stability of the satellite navigation system, the positioning method by BDS and GPS navigation system is presented, the measurement model and the state model are described. Furthermore, the modified square-root Unscented Kalman Filter (SR-UKF) algorithm is employed in BDS and GPS conditions, and analysis of single system/multi-system positioning has been carried out, respectively. The experimental results are compared with the traditional estimation results, which show that the proposed method can perform highly-precise positioning. Especially when the number of satellites is not adequate enough, the proposed method combine BDS and GPS systems to achieve a higher positioning precision.